What Can You Not Take With Rifaximin? Essential Drug and Food Interactions

October 10, 2025 •

4 min read

While rifaximin is minimally absorbed in healthy individuals, its systemic exposure increases significantly in people with liver impairment or when taken with certain other medications. Therefore, it is critical to know what can you not take with rifaximin to ensure the safety and effectiveness of your treatment.

Quick Summary

This guide details key drug, food, and supplement interactions to avoid while taking rifaximin. It explains the risks associated with P-gp inhibitors, warfarin, grapefruit, and alcohol, providing practical advice for medication management.

Key Points

Avoid Cyclosporine and other P-gp Inhibitors: Medications like cyclosporine, clarithromycin, erythromycin, and some HIV drugs significantly increase rifaximin absorption, raising the risk of toxicity.
Do not consume grapefruit: Grapefruit and its juice are potent P-gp inhibitors and can cause a major interaction with rifaximin, leading to dangerously high drug levels.
Monitor warfarin closely: If taking warfarin, rifaximin may alter its blood-thinning effect, requiring close monitoring of your INR and potential dosage adjustments by a doctor.
Limit or avoid alcohol: While not a direct interaction, alcohol can worsen common side effects like nausea and dizziness. It is especially harmful for those with liver disease treated for hepatic encephalopathy.
Space out probiotics: Take probiotics at least 1-2 hours away from your rifaximin dose to prevent the antibiotic from reducing their effectiveness.
Inform your doctor of all medications: Full disclosure of all drugs, supplements, and conditions, especially liver impairment, is crucial to prevent adverse interactions.

Understanding Rifaximin Interactions

Rifaximin (commonly sold as Xifaxan) is an antibiotic primarily used to treat traveler's diarrhea, irritable bowel syndrome with diarrhea (IBS-D), and to prevent hepatic encephalopathy (HE) recurrence. It works by staying mainly within the gastrointestinal tract, allowing it to act locally with minimal systemic absorption in most healthy patients. However, this changes when certain substances are introduced, leading to potentially significant interactions. The primary mechanism for many of these interactions involves a protein called P-glycoprotein (P-gp), which acts as a pump to expel drugs from cells and reduce absorption. Inhibiting this pump can cause rifaximin levels in the bloodstream to increase, raising the risk of side effects. For patients with pre-existing liver conditions, this risk is heightened even further due to the body's reduced ability to process drugs.

Key Medications to Avoid or Monitor Closely

P-glycoprotein (P-gp) Inhibitors

As mentioned, P-gp inhibitors can lead to a significant increase in rifaximin's systemic exposure. Co-administration of a P-gp inhibitor like cyclosporine has been shown to dramatically increase the body's overall exposure to rifaximin, with some studies noting a 124-fold increase.

Examples of P-gp inhibitors to discuss with your doctor include:

Cyclosporine: An immunosuppressant drug that is a major P-gp inhibitor.
Certain Antibiotics: Some macrolides like erythromycin and clarithromycin can increase rifaximin's levels.
Antifungals: Ketoconazole and itraconazole can also inhibit P-gp.
Antivirals: Ritonavir and saquinavir, used for HIV, can lead to higher rifaximin concentrations.
Heart and Blood Pressure Medications: Amiodarone and verapamil have P-gp inhibiting effects.

Warfarin and other Anticoagulants

Rifaximin can alter the blood-thinning effect of warfarin, a common anticoagulant. While the exact mechanism is not fully understood, this interaction can make warfarin less effective or increase the risk of bleeding. Close monitoring of International Normalized Ratio (INR) is essential when both medications are used, and dosage adjustments of warfarin may be necessary.

Other Antibiotics for Travelers' Diarrhea

Using rifaximin alongside other antibiotics commonly prescribed for traveler's diarrhea, such as azithromycin, is not recommended. This combination does not offer additional therapeutic benefits and can increase the risk of side effects.

Fecal Microbiota Products and Certain Vaccines

Some sources suggest that rifaximin may decrease the therapeutic efficacy of fecal microbiota products and attenuated vaccines (like the typhoid vaccine). It is important to inform healthcare professionals about rifaximin use before receiving immunizations.

Food, Drink, and Supplement Interactions

Grapefruit and Grapefruit Juice

Grapefruit is a potent inhibitor of P-glycoprotein, and its consumption can cause a major and dangerous increase in the systemic absorption of rifaximin. Patients are advised to completely avoid grapefruit and grapefruit juice while on this medication.

Alcohol

There is no known direct chemical interaction between rifaximin and alcohol. However, consuming alcohol can worsen certain side effects of rifaximin, such as nausea, headache, and dizziness. For patients with hepatic encephalopathy, alcohol consumption is particularly dangerous as it can trigger an HE episode and worsen liver problems.

Probiotics

Probiotics containing live bacteria, such as Lactobacillus acidophilus or Bifidobacterium infantis, should be taken at least 1 to 2 hours before or after rifaximin. This helps minimize the risk of rifaximin's antibacterial effect reducing the probiotics' effectiveness.

Cannabis and CBD

Cannabis products, including CBD, can inhibit P-glycoprotein, potentially increasing rifaximin exposure and the risk of side effects. If you use cannabis, inform your doctor and pharmacist before starting rifaximin.

What to avoid with rifaximin: A Comparison Table


Substance/Medication	Interaction Type	Risk	Recommended Action
P-gp Inhibitors (Cyclosporine, etc.)	Increased systemic rifaximin absorption	High risk of increased side effects and toxicity, especially with liver impairment	Avoid concomitant use or use with extreme caution and close monitoring
Warfarin	Altered blood-thinning effect	Risk of bleeding or clotting issues	Requires frequent monitoring of INR and potential dosage adjustments
Grapefruit/Grapefruit Juice	P-gp inhibition	Major increase in rifaximin exposure and risk of toxicity	Strict avoidance is necessary
Other Antibiotics (for traveler's diarrhea)	No added benefit, increased adverse effects	Increased side effects without improved outcome	Avoid using in combination for the same condition
Alcohol	Worsening of side effects, exacerbation of liver disease	Increased nausea, dizziness, headache; dangerous for HE patients	Limit or avoid, especially if you have liver issues
Probiotics	Reduced probiotic efficacy	Diminished benefit of probiotic treatment	Separate dosing by 1-2 hours
Cannabis/CBD	P-gp inhibition	Increased systemic rifaximin levels and side effects	Inform your healthcare provider; use with caution

The Importance of Full Medical Disclosure

For any patient taking rifaximin, it is absolutely essential to provide a comprehensive list of all medications, supplements, and herbs to your healthcare provider and pharmacist. This is especially important for those with liver impairment (Child-Pugh Class C), as their body's reduced ability to clear drugs means that even minor interactions can lead to dangerously high rifaximin levels. A thorough review of your medication list can prevent adverse events and ensure your treatment is both safe and effective.

Conclusion

While rifaximin is generally a safe medication due to its low systemic absorption, its safety profile can be significantly altered by certain drug, food, and supplement interactions. The most critical interactions involve P-glycoprotein (P-gp) inhibitors like cyclosporine and grapefruit, which can dramatically increase rifaximin's concentration in the body. Furthermore, patients on blood thinners like warfarin or those with underlying liver conditions must exercise extreme caution. By maintaining open communication with healthcare professionals and carefully managing your other medications and dietary choices, you can minimize risks and ensure that your rifaximin treatment is successful.

Note: This article is for informational purposes only and does not constitute medical advice. Always consult with a healthcare professional before taking or stopping any medication.

Frequently Asked Questions

It is generally not recommended to drink alcohol while taking rifaximin. While there is no direct chemical interaction, alcohol can worsen side effects like nausea and headache. For those with liver disease, it is particularly dangerous and can trigger an episode of hepatic encephalopathy.

Taking cyclosporine with rifaximin is extremely risky. Cyclosporine is a potent P-gp inhibitor that can substantially increase rifaximin's systemic exposure, leading to higher levels in the body and a greater risk of toxicity.

Grapefruit and its juice can interfere with the P-glycoprotein pump in your intestines. By inhibiting this pump, grapefruit dramatically increases the amount of rifaximin that gets absorbed into your body, which can be dangerous.

Rifaximin can alter the effectiveness of warfarin, a blood thinner. This can lead to either an increased or decreased risk of bleeding or clotting. If you are on both medications, your doctor will need to monitor your INR and potentially adjust your warfarin dose.

Yes, but you should space out the doses. Take probiotics at least 1 to 2 hours before or after your rifaximin dose to ensure the antibiotic does not reduce the effectiveness of the live bacteria in the probiotic.

You should not take rifaximin with other antibiotics for the same condition, such as traveler's diarrhea. This will not provide additional benefit and could increase the risk of side effects.

The most significant food interaction is with grapefruit. Otherwise, rifaximin can be taken with or without food. However, patients with certain conditions like IBS-D might feel better avoiding spicy or greasy foods.